Click Reaction-Mediated Fluorescent Immunosensor Based on Cu-MOF Nanoparticles for Ultrasensitive and High-Throughput Detection of Aflatoxin B1 in Food Samples.

Due to the high toxicity of aflatoxin B1 and its risks to human health, we developed a click reaction-mediated automated fluorescent immunosensor (CAFI) for sensitive detection of aflatoxin B1 based on the Cu(I)-catalyzed click reaction. With its large specific surface area, a copper-based metal-organic framework (Cu-MOF) was synthesized to adsorb and enrich the copper ion (Cu(II)) and then load the complete antigen (BSA-AFB1). After the immunoreaction, Cu(II) inside the Cu-MOF-Antigen conjugate would be reduced to Cu(I) in the presence of sodium ascorbate, which triggered the click reaction between the fluorescent donor-modified DNA and the receptor-modified complementary DNA to lead to a fluorescence signal readout. The whole reaction steps were finished by the self-developed automated immunoreaction device. This CAFI method showed a limit of detection (LOD) of 0.48 pg/mL as well as a 670-fold enhancement in sensitivity compared to conventional ELISA, revealing its great potential in practical applications and automated detection.

Efficacy of magnetic therapy for osteoporotic patients: A meta-analysis of randomized controlled studies.

BACKGROUND: Magnetic therapy may have some potential in treating osteoporosis, and this meta-analysis aims to study the efficacy of magnetic therapy for osteoporotic patients. METHODS: We have searched several databases including PubMed, EMbase, Web of Science, EBSCO and Cochrane library databases, and selected the randomized controlled trials comparing the efficacy of magnetic therapy for osteoporotic patients. This meta-analysis was conducted using the random-effect or fixed-effect model based on the heterogeneity. RESULTS: Five randomized controlled trials were included in this meta-analysis. Compared with sham procedure in osteoporotic patients, magnetic therapy was associated with significantly increased bone mineral density (standard mean difference [SMD] = 2.39; 95% confidence interval [CI] = 0.27-4.51; P = .03), decreased pain scores (mean difference [MD] = -0.86; 95% CI = -1.04 to -0.67; P < .00001), and calcium (MD = -0.61; 95% CI = -0.92 to -0.29; P = .0002), but revealed no influence on phosphate (MD = 0.07; 95% CI = -0.30 to 0.44; P = .71), osteocalcin (SMD = 0.65; 95% CI = -2.87 to 4.17; P = .72), or ALP (SMD = -0.43; 95% CI = -0.92 to 0.07; P = .09). CONCLUSIONS: Magnetic therapy may be effective for the treatment of osteoporotic patients.

Influence on the release of arsenic and tungsten from sediment, and effect on other heavy metals and microorganisms by ceria nanoparticle capping.

In this study, ceria nanoparticle (CNP) was used as a capping agent to investigate the efficiency and mechanism of simultaneously controlling the release of sediment internal Arsenic (As) and tungsten (W). The results of incubation experiment demonstrated that CNP capping reduced soluble As and W by 81.80% and 97.97% in overlying water, respectively; soluble As and W by 65.64% and 60.13% in pore water, respectively; and labile As and W in sediment by 45.20% and 53.20%, respectively. The main mechanism of CNP controlling sediment internal As and W was through adsorption via ligand exchange and inner-sphere complexation, as determined through adsorption experiments, XPS and FIRT spectra analysis. Besides, CNP also acted as an oxidant, facilitating the oxidation of AsⅢ to AsV and thereby enhancing the adsorption of soluble As. Additionally, sediment As and W fractions experiments demonstrated that the immobilization of As and W with CNP treatment via transforming mobile to stable fractions was another mechanism inhibiting sediment As and W release. The obtained significant positive correlation between soluble As/W and Fe/Mn, labile As/W and Fe/Mn indicated that iron (Fe) and manganese (Mn) oxidation, influenced by CNP, serve as additional mechanisms. Moreover, Fe redox plays a crucial role in controlling internal As and W, while Mn redox plays a more significant role in controlling As compared to W. Meanwhile, CNP capping effectively prevented the release of As and W by reducing the activity of microorganisms that degrade Fe-bound As and W and reduced the release risk of V, Cr, Co, Ni, and Zn from sediments. Overall, this study proved that CNP was a suitable capping agent for simultaneously controlling the release of As and W from sediment.

Symbiotic hemolymph bacteria reduce hexavalent chromium to protect the host from chromium toxicity in Procambarus clarkii.

Hexavalent chromium (Cr(VI)) is a cytotoxic heavy metal pollutant that adversely affects all life forms. Interestingly, the crustacean Procambarus clarkii exhibits a relatively high tolerance to heavy metals. The underlying mechanisms remain unclear. In this study, we investigated the role of symbiotic bacteria in P. clarkii in alleviating Cr(VI)-induced damage and explored their potential mechanisms of action. Through transcriptomic analysis, we observed that Cr(VI) activated P. clarkii's antimicrobial immune responses and altered the bacterial composition in the hemolymph. After antibiotic treatment to reduce bacterial populations, Cr(VI)-induced intestinal and liver damage worsened, and crayfish exhibited lower levels of GSH/CAT/SOD activity. The Exiguobacterium, the symbiotic bacteria in the hemolymph of P. clarkii, were proved to be primary contributor to Cr(VI) tolerance. Further investigation suggested that it resists Cr(VI) through the activation of the ABC transporter system and the reduction of Cr(VI) via the reductase gene nfsA. To validate the role of Exiguobacterium in Cr(VI) tolerance, crayfish treated with antibiotics then supplemented with Exiguobacterium H6 and recombinant E. coli (with the nfsA gene), reduced Cr(VI)-induced ovarian damage. Overall, this study revealed that the symbiotic bacteria Exiguobacterium can absorb and reduce hexavalent chromium, mitigating Cr(VI)-induced damage in P. clarkii. These findings provide new insights into hexavalent chromium tolerance mechanisms in crustaceans.

Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs.

OBJECTIVE: To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs. METHODS: Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05). CONCLUSION: JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

Impacts of calcium peroxide on phosphorus and tungsten releases from sediments.

In this study, CaO2 was used as a capping material to control the release of Phosphate (P) and tungsten (W) from the sediment due to its oxygen-releasing and oxidative properties. The results revealed significant decreases in SRP and soluble W concentrations after the addition of CaO2. The mechanisms of P and W adsorption by CaO2 were mainly chemisorption and ligand exchange mechanisms. In addition, the results showed significant increases in HCl-P and amorphous and poorly crystalline(oxyhydr)oxides bound W after the addition of CaO2. The highest reduction rates of sediment SRP and soluble W release were 37 and 43%, respectively. Furthermore, CaO2 can promote the redox of iron (Fe) and manganese (Mn). On the other hand, a significant positive correlation was observed between SRP/soluble W and soluble Fe (II) and between SRP/soluble W and soluble Mn, indicating that the effects of CaO2 on Fe and Mn redox play a crucial role in controlling P and W releases from sediments. However, the redox of Fe plays a key role in controlling sediment P and W release. Therefore, CaO2 addition can simultaneously inhibit sediment internal P and W release.

Green synthesis of mesoporous and biodegradable iron silicide nanoparticles for photothermal cancer therapy.

Photothermal nanomaterials have shown great potential for photothermal therapy. In this study, we developed a simple green method of magnesiothermic co-reduction for the synthesis of mesoporous, magnetic and biodegradable iron silicide nanoparticles (FeSi NPs) as applied to photothermal therapy (PTT). Starting from biogenic tabasheer extracted from bamboo and Fe2O3, the resultant FeSi NPs with a much lower band gap exhibited excellent optical absorption with a photothermal conversion efficiency of 76.2%, indicating a good photothermal performance. The weight extinction coefficient was measured to be 13.3 L g-1 cm-1 at 1064 nm (second near-infrared window, NIR-II), which surpassed the performance of other competitive Si-based and Fe-based photothermal agents. Results of the cell viability assay showed that cells could be killed by NIR-II laser irradiation with the synthesized FeSi NPs. In vivo results on mice showed clearly an efficient suppression of tumour growth by photothermal treatment with FeSi NPs. FeSi NPs were found to be biodegradable in simulated body fluids. The results from our work indicate that FeSi NPs are a new class of promising photothermal agents (PTAs) for application in cancer therapy.

Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis.

Objective: Screening out potential herbal medicines and herbal ingredients for the treatment of gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis. Methods: Gene expression profiles of gastric tumour tissues and normal tissue samples were obtained from the GEO database and the samples were analysed for immune cell infiltration condition and differential expressed genes of ferroptosis. Key genes were screened by protein-protein interaction (PPI) and enrichment analysis, and molecular docking was used to predict and preliminary validate potential herbal and traditional Chinese medicine components for gastric cancer based on the key genes. Finally, RT-QPCR was used to validate the prediction results. Results: Immune cell infiltration analysis revealed high levels of infiltration of activated CD4 memory T cells, monocytes, M0 macrophages in gastric tumor tissues, while plasma cells and resting mast cells had higher levels of infiltration in the paraneoplastic tissues. Differential gene expression analysis identified 1,012 upregulated genes and 880 downregulated genes, of which 84 immune related differentially expressed genes such as CTSB, PGF and PLAU and 10 ferroptosis-related differentially expressed genes such as HSF1, NOX4 and NF2 were highly expressed in gastric cancer tissues. The results of enrichment analysis showed that they mainly involve 343 biological processes such as extracellular matrix organization and extracellular structural organization; 37 cellular components such as complexes of collagen trimer and basement membrane; 35 molecular functions such as signal receptor activator activity and receptor ligand activity; 19 regulatory pathways such as cytokine-cytokine receptor interactions and retinol metabolism. Finally, two key genes, TLR4 and KRAS, were selected and 12 herbal medicines such as Radix Salviae liguliobae, Rhizoma Coptidis, Rhizoma Polygoni cuspidati and 27 herbal ingredients such as resveratrol, salvianolic acid b were predicted on the basis of key genes. Molecular docking results showed that KRAS binds tightly to coumarin and magnolol, while TLR4 can bind tightly to resveratrol, curcumin, salvianolic acid b, shikonin. Subsequently, the effect of resveratrol and magnolol was experimentally verified. Conclusion: Herbal medicines such as S. liguliobae, Rhizoma Coptidis, Rhizoma P. cuspidati and herbal ingredients such as resveratrol, curcumin, salvianolic acid b may provide research directions and alternative therapeutic approaches for immunomodulation of TME and ferroptosis of tumour cells in gastric cancer.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice.

BACKGROUND: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. METHODS: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. FINDINGS: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. INTERPRETATION: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. FUNDING: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.

Improved 31P NMR analysis of phosphorus in highly mineralized lake water using a modified pretreatment procedure with H resin.

31P Nuclear Magnetic Resonance (31P NMR) is an important analytical tool for identifying and quantifying phosphorus-based compounds in aquatic environments. However, the precipitation method typically used for analyzing phosphorus species via 31P NMR has limited application. To expand the scope of the method and apply it to highly mineralized rivers and lakes worldwide, we present an optimization technique that employs H resin to assist phosphorus (P) enrichment in highly mineralized lake water. To explore how to reduce analysis interference from salt in highly mineralized water and improve the accuracy of P analysis using 31P NMR, we conducted case studies on Lake Hulun and Qing River. This study aimed to increase the efficiency of phosphorus extraction in highly mineralized water samples by using H resin and optimizing key parameters. The optimization procedure included determining the enriched water volume, H resin treatment time, AlCl3 addition amount, and precipitation time. The final recommended optimization enrichment procedure involves treating 10 L of filtered water sample with 150 g of Milli-Q water-washed H resin for 30 s, adjusting the pH of the treated sample to 6-7, adding 1.6 g of AlCl3, stirring the mixture, and allowing the solution to settle for 9 h to collect the flocculated precipitate. The precipitate was then extracted with 30 mL of 1 M NaOH +0.05 M DETA extraction solution at 25 °C for 16 h, and the supernatant was separated and lyophilized. The lyophilized sample was redissolved in 1 mL of 1 M NaOH +0.05 M EDTA. This optimized analytical method using 31P NMR effectively identified phosphorus species in highly mineralized natural waters and can be applied to other highly mineralized lake waters globally.

Sulfur disproportionation realizes an organic-free sulfidogenic process for sustainable treatment of acid mine drainage.

Biological sulfidogenic processes (BSPs) have been considered effective biotechnologies for the treatment of organic-deficit acid mine drainage (AMD) and heavy metal recovery. However, high-rate sulfide production relies on the continuous addition of exogenous organic substrates as electron donors to facilitate dissimilatory sulfate reduction, which substantially increases the operational cost and CO2 emission and also limits the wide application of BSPs in AMD treatment. In this study, we proposed a novel chemoautotrophic elemental sulfur disproportionation (SD) process as an alternative to conventional BSPs for treating AMD, in which sulfur-disproportionating bacteria (SDB) disproportionates sulfur to sulfide and sulfate without organic substrate supplementation. During the 393-day lab-scale test, we observed that the sulfur-disproportionating reactor (SDR) achieved a stable high-rate sulfide production, with a maximal rate of 21.10 mg S/L-h at an organic-substrate-free condition. This high rate of sulfide production suggested that the SD process could provide sufficient sulfide to precipitate metal ions from AMD. Thermodynamics analysis and batch tests further revealed that alkalinity rather than sulfate was the critical factor influencing the SD process, suggesting that the abundant sulfate present in AMD would not inhibit the SD process. The critical condition of SD in the SDR was therefore determined. Microbial community analysis showed that Dissulfurimicrobium sp. was the dominant SDB during the long-term operation regardless of dynamic sulfate and/or alkalinity concentrations, which provides evidence that SDB can be employed for sustainable and high-rate sulfide production for engineering purposes. A multi-stage AMD treatment system equipped with a SDR removed over 99% of the influent metals (i.e., Fe, Al, Zn, Cu, Pb) from AMD except for Mn. This study demonstrated that the novel SD process is a green and promising biotechnology for the sustainable treatment of organic-deficient metal-laden wastewater, such as AMD.

Fully biobased sustainable elastomers derived from chitin, lignin, and plant oil via grafting strategy and Schiff-base chemistry.

With the dramatically increased environmental problems, the rational design of sustainable polymers from renewable feedstocks opens new avenues to reduce the huge pollution impact. The major challenge for sustainable polymers is the decreased mechanical performance compared to that of petroleum-based materials. In this work, fully biobased sustainable elastomers were developed by integrating renewable chitin, lignin, and plant oil into one macromolecule, in which chitin was chosen as the rigid backbone, while a lignin-derived monomer vanillin acrylate (VA) and a plant oil-based monomer lauryl acrylate (LA) were selected as the hard and soft segments for the grafted side chains. A series of Chitin-graft-poly(vanillin acrylate-co-lauryl acrylate) (Chitin-g-P(VA-co-LA)) copolymers with varied feed ratios and chitin contents were synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization as an effective grafting strategy. In addition, a dynamic cross-linked network was incorporated via Schiff-base reaction to improve the macroscopic behavior of such kind of chitin graft elastomers. These sustainable elastomers are mechanically strong and show excellent reprocessablity, as well as outstanding UV-blocking property. This strategy is versatile and can inspire the further development of fully biobased sustainable materials from natural resources.

Effects of dietary oat supplementation on carcass traits, muscle metabolites, amino acid profiles, and its association with meat quality of Small-tail Han sheep.

Oat supplementation of the ruminant diet can improve growth performance and meat quality traits, but the role of muscle metabolites has not been evaluated. This study aimed to establish whether oat grass supplementation (OS) of Small-tail Han sheep improved growth performance and muscle tissue metabolites that are associated with better meat quality and flavor. After 90-day, OS fed sheep had higher live-weight and carcass-weight, and lower carcass fat. Muscle metabolomics analysis showed that OS fed sheep had higher levels of taurine, l-carnitine, inosine-5'-monophospgate, cholic acid, and taurocholic acid, which are primarily involved in taurine and hypotaurine metabolism, purine metabolism, and bile acid biosynthesis and secretion, decreased fat accumulation and they promote functional or flavor metabolites. OS also increased muscle levels of amino acids that are attributed to better quality and flavorsome mutton. These findings provided further evidence for supplementing sheep with oat grass to improve growth performance and meat quality.

Wumei Wan attenuates angiogenesis and inflammation by modulating RAGE signaling pathway in IBD: Network pharmacology analysis and experimental evidence.

BACKGROUND: Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism of its action remains to be further clarified. PURPOSE: To investigate the underlying mechanisms of WMW in the treatment of chronic ulcerative colitis (UC) through network pharmacology and experimental validation. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform were used to identify the ingredients and potential targets of WMW. The microarray gene data GSE75214 datasets from GEO database was used to define UC-associated targets. Cytoscape3.7.2 was employed to construct the protein-protein interaction (PPI) network and compounds-disease targets network. GO enrichment analysis and KEGG pathway analysis were performed by R software for functional annotation. UPLC-TOF-MS/MS method was used to quantitatively analyze the active ingredients of WMW. For experimental validation, three cycles of 2% dextran sulfate sodium salt (DSS) were used to construct chronic colitis model. The hub targets and signal pathway were detected by qPCR, ELISA, western blotting , immunohistochemical and immunofluorescence. RESULTS: Through network analysis, 104 active ingredients were obtained from WMW, and 47 of these ingredients had potential targets for UC. A total of 41 potential targets of WMW and 13 hub targets were identified. KEGG analysis showed that WMW involved in advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, and luteolin of WMW were the more highly predictive components related to the AGE-RAGE signaling pathway. In vivo validation, WMW improved DSS-induced colitis, reduced the expression of inflammatory cytokines and chemokines. Notably, it significantly decreased the mRNA expression of Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr and Icam1, which were associated with angiogenesis. In addition, we confirmed WMW inhibited RAGE expression and diminished DSS-induced epithelial barrier alterations CONCLUSION: Our results initially demonstrated the effective components and the strong anti-angiogenic activity of WMW in experimental chronic colitis. Sufficient evidence of the satisfactory anti-colitis action of WMW was verified in this study, suggesting its potential as a quite prospective agent for the therapy of UC.

Indirect treatment of plasma-processed air to decrease decay and microbiota of strawberry fruit caused by mechanical damage.

Due to the soft texture of strawberry fruit, it is highly susceptible to mechanical damage during postharvest supply chains, resulting in decay and quality deterioration. Urgent investigation is needed on the treatment techniques to mitigate the impact of postharvest mechanical damage of strawberry fruit. In the present study, the effect of indirect plasma-processed air (PPA) pretreatment to decrease decay and microbiota of strawberry fruit caused by mechanical damage was investigated. The results show PPA pretreatment reduced the total counts of indigenous microbiota on the surface of intact and mechanical damaged strawberry fruit by 4.29 and 3.76 log10CFU/g at day 0, respectively, and reduced the counts of S. aureus and E. coli inoculated on strawberry fruit by 3.05-3.16 and 3.55-3.56 log10CFU/g, respectively. The disease incidence of fruit inoculated with Botrytis cinerea was also decreased by 6.67 %-18.89 % during storage. Besides, PPA pretreatment reduced the decay rate of strawberry fruit by 5.56 %-21.11 % during storage and did not significantly affect the firmness, color index of red grapes (CIRG) and total soluble solids (TSS) content of strawberry fruit. DHHP results indicate that the antioxidant activity of the strawberry fruit was increased. After PPA pretreatment, 39 metabolites were differentially accumulated in strawberry fruits, 37 of which were up-regulated, including flavonoids, phenolic acids and organic acid.

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/ß-catenin pathway in the myocardium of mice after myocardial infarction.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/ß-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/ß-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.

Effects and mechanisms of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide from Safflower on endothelial injury in vitro and on thrombosis in vivo.

Background: The florets of Carthamus tinctorius L. (Safflower) is an important traditional medicine for promoting blood circulation and removing blood stasis. However, its bioactive compounds and mechanism of action need further clarification. Objective: This study aims to investigate the effect and possible mechanism of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide (HGG) from Safflower on endothelial injury in vitro, and to verify its anti-thrombotic activity in vivo. Methods: The endothelial injury on human umbilical vein endothelial cells (HUVECs) was induced by oxygen-glucose deprivation followed by reoxygenation (OGD/R). The effect of HGG on the proliferation of HUVECs under OGD/R was evaluated by MTT, LDH release, Hoechst-33342 staining, and Annexin V-FITC apoptosis assay. RNA-seq, RT-qPCR, Enzyme-linked immunosorbent assay and Western blot experiments were performed to uncover the molecular mechanism. The anti-thrombotic effect of HGG in vivo was evaluated using phenylhydrazine (PHZ)-induced zebrafish thrombosis model. Results: HGG significantly protected OGD/R induced endothelial injury, and decreased HUVECs apoptosis by regulating expressions of hypoxia inducible factor-1 alpha (HIF-1α) and nuclear factor kappa B (NF-κB) at both transcriptome and protein levels. Moreover, HGG reversed the mRNA expression of pro-inflammatory cytokines including IL-1ß, IL-6, and TNF-α, and reduced the release of IL-6 after OGD/R. In addition, HGG exhibited protective effects against PHZ-induced zebrafish thrombosis and improved blood circulation. Conclusion: HGG regulates the expression of HIF-1α and NF-κB, protects OGD/R induced endothelial dysfunction in vitro and has anti-thrombotic activity in PHZ-induced thrombosis in vivo.

Effects of a natural nutritional supplement on immune cell infiltration and immune gene expression in exercise-induced injury.

Inflammatory immune response plays a key role in exercise-induced injury and healing; however, the relevant regulatory mechanisms of immune infiltration in exercise-induced injuries remain less studied. In the present study, a highly efficient system for screening immunity-related biomarkers and immunomodulatory ability of natural nutritional supplements was developed by integrating intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. The findings demonstrated that resting natural killer cells showed a higher rate of infiltration after exercise, whereas naive B cells and activated dendritic cells showed higher rate of infiltration before exercise. Four key genes, namely PRF1, GZMB, CCL4, and FASLG, were associated with exercise-induced injuries and inflammatory immune response. In total, 26 natural compounds including echinacoside, eugenol, tocopherol, and casuariin were predicted by using the HERB databases. Molecular docking analysis showed that GZMB, FASLG, and CCL4 bound to echinacoside. In vivo experiments in mice showed that after 30 min swimming, natural killer (NK) cells showed high infiltration rates, and the key genes (GZMB, PRF1, FASLG, and CCL4) were highly expressed; however, echinocandin significantly reduced the level of NK cells and decreased the expression of the four key genes post exercise. This natural nutritional supplement may act to protect against inflammatory injury after exercise by suppressing specific immune infiltration.

Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation.

Inflammatory immune response is apparently one of the determinants of progressive exacerbation of valvular atrial fibrillation(VAF). Ferroptosis, an iron-dependent modality of regulated cell death, is involved in the immune regulation of cardiovascular disease. However, the relevant regulatory mechanisms of immune infiltration and ferroptosis in VAF have been less studied. In the current study, a highly efficient system for screening immunity- and ferroptosis-related biomarkers and immunomodulatory ability of herbal ingredients has been developed with the integration of intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. VAF patients showed higher infiltration of neutrophils and resting stage dendritic cells, while VSR patients showed higher infiltration of follicular helper T cells. In addition, six (e.g., PCSK2) and 47 (e.g., TGFBR1) ImmDEGs and one (SLC38A1) and four (TGFBR1, HMGB1, CAV1, and CD44) FerDEGs were highly expressed in patients with valvular sinus rhythm (VSR) and VAF, respectively. We further identified a core subnetwork containing 34 hub genes, which were intersected with ImmDEGs and FerDEGs to obtain the key gene TGFBR1. Based on TGFBR1, 14 herbs (e.g., Fructus zizyphi jujubae, Semen Juglandis, and Polygonum cuspidatum) and six herbal ingredients (curcumin, curcumine, D-glucose, hexose, oleovitamin A, and resveratrol) were predicted. Finally, TGFBR1 was found to dock well with curcumin and resveratrol, and it was further verified that curcumin and resveratrol could significantly reduce myocardial fibrosis. We believe that herbs rich in curcumin and resveratrol such as Rhizoma curcumae longae and Curcuma kwangsiensis, mitigate myocardial fibrosis to improve VAF by modulating the TGFß/Smad signaling pathway. This strategy provides a prospective approach systemically characterizing phenotype-target-herbs relationships based on the tissue-specific biological functions in VAF and brings us new insights into the searching lead compounds from Chinese herbs.

Maternal propionate supplementation ameliorates glucose and lipid metabolic disturbance in hypoxia-induced fetal growth restriction.

Intrauterine growth restriction (IUGR), one of the major complications of pregnancy, is characterized by low birth weight and results in higher risks for long-term problems including developing metabolic and cardiovascular diseases. Short-chain fatty acids (SCFAs), especially propionate, have been reported to correct glucose and lipid disorders in metabolic diseases. We hypothesized that maternal propionate supplementation could prevent glucose and lipid metabolic disturbance in hypoxia-induced IUGR. Here, in our study, maternal hypoxia was induced from gestational day (GD) 11 to GD 17.5 to establish an IUGR mouse model. Maternal propionate treatment reversed reduced birth weight in male IUGR offspring. Hepatic transcriptomics demonstrated that SP treatment significantly lowered glucose and lipid metabolism-related genes (Scd1, G6pc, Pck1 and Fasl) in IUGR offspring. KOG enrichment analysis showed that propionate-induced down-regulated differential expressed genes (DEGs) mainly belonged to lipid transport and metabolism. KEGG enrichment results showed that the down-regulated DEGs were mostly enriched in PPAR and FoxO signaling pathways. We also found that maternal oral administration of SP decreased serum lipid content, attenuated hepatic insulin resistance and liver lipid accumulation, reduced hepatic key gene expressions of gluconeogenesis and lipogenesis, increased energy expenditure and improved liver function in 11-week-old male IUGR offspring. These results indicate that maternal propionate supplementation increases birth weight and corrects hepatic glucose and lipid metabolic disturbance and energy expenditure in male mice born with IUGR, which may provide a basis for using propionate to treat IUGR disease.